Primary liver cancer is currently the fifth most common cause of cancer deaths among men, and ninth among women in the US, with the numbers increasing yearly. The most recent data indicate that in 2008 there were an estimated 21,370 new cases of liver and bile duct cancer of which the majority are hepatocellular carcinomas (HCCs), with 18,410 deaths (Institute, N.C., SEER Cancer Statistics Review, 1975-2005, Ries L A G, et al., Editors. 2008.). Worldwide, it is the fourth most common cancer, with approximately 663,00 fatal cases reported in 2008; based on current trends and baseline models, the incidence is expected to rise to 756,000 in 2015, and 955,000 in 2030 (Mathers, C. D. and D. Loncar, Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med, 2006. 3, 11, p. e442.). Although it is comparatively uncommon in the US, its incidence has been rising over the last 20 years partially as a result of burgeoning numbers of cases of chronic hepatitis C (Caldwell, S. and S. H. Park, The epidemiology of hepatocellular cancer: from the perspectives of public health problem to tumor biology. J Gastroenterol, 2009. 44 Suppl 19: p. 96-101. El-Serag, H. B., et al., The continuing increase in the incidence of hepatocellular carcinoma in the United States: an update. Ann Intern Med, 2003. 139(10): p. 817-23) one of the principal causes along with hepatitis B and aflatoxin exposure.
There is a long felt need for new drugs that are both disease-modifying and effective in treating patients with primary liver cancer, including but not limited to hepatocellular carcinoma, hepatoblastoma, and cholangiocarcinoma. There is also a clear and present need for new therapeutic agents that are both disease modifying and effective in treating patients that are infected with a hepatitis virus. The present invention addresses the need for new drugs that are both disease-modifying and effective in treating patients suffering from primary liver cancer and hepatocellular carcinoma. Because the present invention targets the cell types that have been demonstrated to support viral infection in the liver, the present invention addresses also the need for new antiviral drugs that are both disease-modifying and effective in treating patients that are infected with hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus, and hepatitis E virus., as well as other viral species that infect the liver.